Substituted cinchona alkaloids have long been known for their profound physiological activity. For example, U.S. Pat. No. 3,663,552 discloses substituted quinine, quinidine, cinchonine and cinchonidine for use as antimalarial and antiarrhythmic compounds. An improved method of preparing these compounds is disclosed in U.S. Pat. No. 3,823,146.
Cupreidine is mentioned as a theoretical compound in U.S. Pat. No. 2,033,679 filed Feb. 27, 1934. The patentees do not disclose or claim to have synthesized the compound, however. In 1933 Ludwiczakowna et al. claimed the synthesis of cupreidine by demethylation through treating with sulfuric acid. 52 Rec. Trav. Chim. p. 847 (1933). It was later proven that the demethylation reaction carried out by Ludwiczakowna et al. does not yield cupreidine but, instead, dihydrocupreidine. Henry and Solomon, J. Chem. Soc., 1934, p. 1924.
Quinidine has remained one of the most important and efficacious drugs for maintaining normal heart rhythm notwithstanding significant side effects associated with its use. Quinidine has two structural groups that are potentially reactive. Thus, efforts have been made to synthesize quinidine derivatives which would have useful therapeutic activity with a lower level of toxicity than quinidine. These efforts have met with very limited success.